Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 424, Issue 1, Pages 53-58Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/S0014-2999(01)01111-6
Keywords
trigeminovascular; migraine; headache; adrenergic compound
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The pharmacology of neurogenic trigeminovascular vasodilator responses in the dura mater is of interest for understanding the pathophysiology of migraine and to develop new therapies for this disabling common condition. Aminergic mechanisms have been implicated in migraine through direct study of amines in patients, and by inference from the pharmacology of many effective anti-migraine compounds, particularly preventative agents. This study used intravital microscopy to assess the role of aminergic transmission in neurogenic dural vasodilatation (NDV) by measuring directly the diameter of dural arteries in sodium pentobarbitone anaesthetised rats. Electrical stimulation of a closed cranial window produces, by local depolarisation of nerves, dural vessel dilation that is monitored continuously on-line using video-microscopy and a video dimension analyser. This dural vasodilatation was not affected by pre-treatment with an alpha (1)-adrenoceptor agonist (phenylephrine, 1 and 5 mug/kg), or antagonist (corynanthine, 1 and 2 mg/kg), nor by an alpha (2)-adrenoceptor agonist (UK14,304, 5 mug/kg) or antagonist (yohimbine, 1 and 3 mg/kg). Similarly, we saw no effect of beta -adrenoceptor blockade (propranolol, 1 and 3 mg/kg). The lack of an inhibitory effect of UK14,304 the model of neurogenic dural vasodilation contrasts with its effect in neurogenic dural plasma protein extravasation model. The lack of inhibition of beta -adrenoceptor antagonists in the neurogenic vasodilatation model contrasts with their usefulness as migraine prophylactics, and suggests that their mechanism of action in migraine is unlikely to be through sensory trigeminal fibre terminals at the neurovascular junction. Moreover, the data indicate that the adrenergic system does not play a significant role in neurogenic dural vasodilation. (C) 2001 Elsevier Science B.V. All rights reserved.
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